Association of variants at UMOD with chronic kidney disease and kidney stones-role of age and comorbid diseases.
PLoS Genet
; 6(7): e1001039, 2010 Jul 29.
Article
em En
| MEDLINE
| ID: mdl-20686651
ABSTRACT
Chronic kidney disease (CKD) is a worldwide public health problem that is associated with substantial morbidity and mortality. To search for sequence variants that associate with CKD, we conducted a genome-wide association study (GWAS) that included a total of 3,203 Icelandic cases and 38,782 controls. We observed an association between CKD and a variant with 80% population frequency, rs4293393-T, positioned next to the UMOD gene (GeneID 7369) on chromosome 16p12 (OR = 1.25, P = 4.1x10(-10)). This gene encodes uromodulin (Tamm-Horsfall protein), the most abundant protein in mammalian urine. The variant also associates significantly with serum creatinine concentration (SCr) in Icelandic subjects (N = 24,635, P = 1.3 x 10(-23)) but not in a smaller set of healthy Dutch controls (N = 1,819, P = 0.39). Our findings validate the association between the UMOD variant and both CKD and SCr recently discovered in a large GWAS. In the Icelandic dataset, we demonstrate that the effect on SCr increases substantially with both age (P = 3.0 x 10(-17)) and number of comorbid diseases (P = 0.008). The association with CKD is also stronger in the older age groups. These results suggest that the UMOD variant may influence the adaptation of the kidney to age-related risk factors of kidney disease such as hypertension and diabetes. The variant also associates with serum urea (P = 1.0 x 10(-6)), uric acid (P = 0.0064), and suggestively with gout. In contrast to CKD, the UMOD variant confers protection against kidney stones when studied in 3,617 Icelandic and Dutch kidney stone cases and 43,201 controls (OR = 0.88, P = 5.7 x 10(-5)).
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Variação Genética
/
Cálculos Renais
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Insuficiência Renal Crônica
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Estudo de Associação Genômica Ampla
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Uromodulina
Tipo de estudo:
Etiology_studies
/
Observational_studies
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Risk_factors_studies
Limite:
Humans
País como assunto:
Europa
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article